Abstract
6-O-Carboxypropyl-alpha-tocotrienol (α-T3E) is an anti-cancer agent that exhibits cytotoxicity against cancer cells, including malignant mesothelioma (MM) cells. However, the mechanism underlying this cytotoxicity remains unclear and we have studied to explain this mechanism. In the study, we demonstrated that α-T3E broke proteasome homeostasis thought simultaneous inhibition of signal transducer and activator of transcription 3 (STAT3) and nuclear respiratory factor 1 (NRF1) in MM cells and that α-T3E induced endoplasmic reticulum (ER) stress, which induces cell death to cancer cells, in MM cells. These results indicate that α-T3E exhibits cytotoxicity against cancer cells by inhibiting proteasome function and inducing ER stress. In this review, we summarize the proteasome inhibitory effect of α-T3E and explain the effectiveness of α-T3E in MM therapy.
